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Understanding the slow depletion of memory CD4(+) T cells in HIV infection

Yates, A; Stark, J; Klein, N; Antia, R; Callard, R; (2007) Understanding the slow depletion of memory CD4(+) T cells in HIV infection. PLoS Medicine , 4 (5) , Article e177. 10.1371/journal.pmed.0040177. Green open access

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Abstract

Background The asymptomatic phase of HIV infection is characterised by a slow decline of peripheral blood CD4(+) T cells. Why this decline is slow is not understood. One potential explanation is that the low average rate of homeostatic proliferation or immune activation dictates the pace of a "runaway'' decline of memory CD4(+) T cells, in which activation drives infection, higher viral loads, more recruitment of cells into an activated state, and further infection events. We explore this hypothesis using mathematical models.Methods and Findings Using simple mathematical models of the dynamics of T cell homeostasis and proliferation, we find that this mechanism fails to explain the time scale of CD4(+) memory T cell loss. Instead it predicts the rapid attainment of a stable set point, so other mechanisms must be invoked to explain the slow decline in CD4(+) cells.Conclusions A runaway cycle in which elevated CD4(+) T cell activation and proliferation drive HIV production and vice versa cannot explain the pace of depletion during chronic HIV infection. We summarize some alternative mechanisms by which the CD4(+) memory T cell homeostatic set point might slowly diminish. While none are mutually exclusive, the phenomenon of viral rebound, in which interruption of antiretroviral therapy causes a rapid return to pretreatment viral load and T cell counts, supports the model of virus adaptation as a major force driving depletion.

Type: Article
Title: Understanding the slow depletion of memory CD4(+) T cells in HIV infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pmed.0040177
Publisher version: http://dx.doi.org/10.1371/journal.pmed.0040177
Language: English
Additional information: © 2007 Yates et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: IMMUNODEFICIENCY-VIRUS TYPE-1, ACTIVE ANTIRETROVIRAL THERAPY, IN-VIVO, GASTROINTESTINAL-TRACT, DISEASE PROGRESSION, POPULATION BIOLOGY, LYMPHATIC TISSUES, IMMUNE ACTIVATION, BYSTANDER CELLS, LYMPHOID-TISSUE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/99470
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